SNP-its Study Summaries

The University of Florida Health Personalized Medicine Program has released "SNP-its" study summaries for pharmacogenomic articles with clinical relevance.    The editorial team reviews articles from multiple journals and writes summaries for the ones most relevant to practicing clinicians.  Those interested are welcome to subscribe to a monthly newsletter.  Online, readers can browse summaries by topic. 

In the first newsletter, SNP-its highlights articles about

•  CYP2C19 poor metabolizers may need a four-fold dose increase for clopidogrel
•  CYP2D6  drug interactions may decrease response to hydrocodone and increase response to ondansetron
•  personalized medicine in cardiology and oncology in Europe.

They also provide an overview of the personalized medicine program at UF Health.

PharmGKB is pleased to work with the SNP-its initiative to highlight articles with these summaries on our website in the coming weeks.  Look for the SNP-its icon on PharmGKB!

CPIC PEG interferon-alpha guideline now available on guideline.gov

More CPIC PGx-based dosing guidelines are now available on the National Guideline Clearinghouse (NGC) website.  NGC is a public resource for evidence-based clinical guidelines, an initiative of the Agency for Healthcare Research and Quality, US Department of Health Services.
The most recent CPIC guideline on NGC is:
Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for IFNL3 (IL28B) genotype and PEG interferon-α–based regimens.

View 10 CPIC guidelines on the NGC website: 

• CYP2D6, CYP2C19 & tricyclic antidepressants
• CYP2D6 & codeine
• CYP2C19 & clopidogrel
• TPMT & thiopurines
• HLA-B & allopurinol
• HLA-B & abacavir
• HLA-B & carbamazepine
• SLCO1B1 & simvastatin
• DYPD & fluoropyrimidine
• IFNL3/IL28B & peginterferon alpha

Read more about CPIC and view all PGx-based dosing guidelines available on PharmGKB.

New CPIC Guideline: CYP2C9, HLA-B and Phenytoin

Guidelines regarding the use of pharmacogenomic tests for CYP2C9 and HLA-B in dosing phenytoin have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC).

Phenytoin is broadly used to treat epilepsy, but it has a narrow therapeutic index and wide inter-patient variability.  Much of this variability is due to genetic variations in CYP2C9 and dosing levels can be altered based on patient genotype.  Additionally, HLA-B*15:02 is associated with an increased risk of phenytoin-induced cutaneous adverse drug reactions, and it is recommended that patients with at least one copy of this variant allele receive an alternate drug.

For details, see the CPIC guideline on PharmGKB.
 
For other CPIC guidelines see the list of CPIC publications and guidelines in progress.

PGx of anti-HIV drug described in new PharmGKB pathway

Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor used as part of a highly active anti-retroviral therapy (HAART) regimen against HIV-1 infection. Large variability in EFV plasma levels is observed between patients given the same dose. Genetic variants underlying EFV metabolism have been shown to contribute to this variability.

A new PharmGKB pathway depicts the inhibitory action of EFV on HIV replication in T cells and the genes involved in metabolism of the drug in human hepatocytes. Associations between variants in these genes and EFV exposure, toxicity and efficacy are discussed in the pathway description. 

> View the PharmGKB Efavirenz Pathway, PK/PD